Cytokines are a unique family of growth factors. Secreted primarily from leukocytes, cytokines stimulate both the humoral and cellular immune responses, as well as the activation of phagocytic cells. Cytokines secreted from lymphocytes are termed lymphokines, whereas those secreted by monocytes or macrophages are termed monokines. Many of the lymphokines are also known as interleukins (IL's), since they are not only secreted by leukocytes, but are also able to affect the cellular responses of leukocytes. Specifically, interleukins are growth factors targeted to cells of hematopoietic origin. One of the interleukins, IL-12, is a pro-inflammatory cytokine interleukin. This cytokine is predominantly secreted either as a αβ heterodimeric form or as a ββ homodimeric form. Both dimer forms bind the IL-12-receptor on target cells but differ in the spectrum of biological activities induced. The αβ form is crucial for generation of cell-mediated immunity against parasites, viruses and bacteria, but contributes also to destructive effects in pathogenesis of autoimmune diseases, e.g. MS, RA and inflammatory bowel disease. The ββ form has been shown to be instrumental in virus-induced inflammation, and in excessive epithelial airway inflammation seen in asthma. Thus, both forms of IL-12 are disease-promoting factors in a variety of conditions. Recently, two novel cytokines have been discovered, named interleukin-23 and interleukin-27 that apparantly belong to the IL-12 subclass of cytokines based on structural relationships. Both IL-23 and IL-27 share with IL-12 a typical heterodimeric structure and are invloved in a similar array of immune responses.
Celebrex is a diaryl-substituted pyrazole. It is a nonsteroidal anti-inflammatory drug (NSAID) that is indicated for the treatment of osteoarthritis, rheumatoid arthritis, for the management of acute pain in adults for the treatment of primary dysmenorrhea. The mechanism of action of CELEBREX is believed to be due to inhibition of prostaglandin synthesis, primarily via inhibition of cyclooxgenase-2 (COX-2). Scientific literature indicates that CELEBREX displays antitumor effects by sensitizing cancer cells to apoptosis. A recent paper has indicated that CELEBREX blocks the endoplasmic reticulum (ER) Ca2+-ATPases, and it has been suggested that this Ca2+ perturbation may be part of the signaling mechanism by which CELEBREX triggers apoptosis. This Ca2+ perturbation effect seems to be unique to CELEBREX and was not seen with any of the other COX inhibitors (e.g. aspirin, ibuprofen, naproxen etc.)